Retroprogesterones are a class of steroids with hormonal activity used in the therapy and treatment of female genital tract dysfunctions and in pregnancy.
The parent compound of the family is retroprogesterone, a compound having a 4-ring steroid structure of the type shown in the following figure:
wherein the spatial orientation of the hydrogen atoms at positions 8 and 9 is beta while that of methyl at position 10 is alpha; this structure differs from that of progesterone, having the configuration referred to as “natural” shown in the following figure, in the opposite orientation of the hydrogen atom at position 9 (alpha) and the methyl one at position 10 (beta).

Retroprogesterones useful in the therapeutic field are for example dydrogesterone and trengestone, having the following structural formulas:

Dydrogesterone has proven effective in treating various conditions associated with a deficiency of progesterone, including infertility due to luteal insufficiency, miscarriage (threatened or recurrent), menstrual disorders, premenstrual syndrome and endometriosis, while trengestone has been employed for the treatment of disorders related to the menstrual cycle.
An intermediate useful in the synthesis of retroprogesterones is the compound of the following formula (1), whose chemical name is 17β-hydroxy-des-A-androst-9,10-en-5-one:
described in J. Org. Chem, 32, 3008 (1967); the use of the compound as a synthesis precursor of retroprogesterones is reported in J. Org. Chem, 33 (9), 1968.
Compound (1) can be synthesized according to the recipes given in J. Org. Chem, 32, 3008 (1967) starting from the bicyclic intermediate (2) with a series of chemical reactions leading to the racemic mixture of compound (1):

Such a racemic mixture cannot be used as such for the preparation of retroprogesterones since it is a mixture of the two optical antipodes.
In the cited article, the authors also report that compound (1) had been previously obtained in the “optically active” form by chemical degradation of testosterone acetate. This method has only scientific value, as it allowed to obtain the optically pure product for the first time but it is not applicable to an industrial production of steroids: in fact, testosterone acetate (4 ring backbone) should be synthesized and the first ring (3 ring backbone) should be degraded and then rebuilt.
The preparation of the compound of formula (1) in optically active form is described in Tetrahedron vol. 24, pp. 2039-2046, 1968; according to the method described, starting from the racemic intermediate (3) and resolving the optical antipodes in the course of the synthesis with brucine salts, compound (1) in optically pure form is obtained:

Although this synthesis is applicable for the preparation of retroprogesterones, it has the drawback of starting from a racemic reagent; the resolution of a racemate, even in the ideal case of quantitative separation yield, leads to a maximum of 50% yield.
In J MED CHEM 1985, 28, 1796-1803, scheme (I), compounds of general structure (5) are prepared in order to study them and verify their potential pharmacological activity. According to the teachings of the article, these compounds can be prepared starting from precursor (4):

In turn, the compounds of general formula (4) can be prepared, as described in U.S. Pat. No. 3,413,314, by total synthesis according to scheme:

This route of synthesis, however, also has the problem that one of the steps (U.S. Pat. No. 3,413,314, column 2, step d) consists in the separation of the optical antipodes by salification with a chiral amine, with consequent loss of at least half of the starting material.
It is the object of the present invention to provide an improved synthesis route for the preparation of 17β-hydroxy-des-A-androst-9,10-en-5-one, in particular simpler than the prior art processes and industrially applicable.